Venous Leg Ulcer (VLU)Phase 4VaLUe INCT06754735
Trial to Evaluate Cyclical Topical Wound Oxygen Therapy in the Treatment of Chronic Venous Leg Ulcers
A Phase 4 study testing Topical Wound Oxygen Therapy in people with Venous Leg Ulcer (VLU), run by AOTI Ltd. at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the efficacy, safety and economic benefits of Cyclical Pressure Topical Wound Oxygen (TWO2) Therapy in the treatment of venous leg ulcers. Participants will utilize standard of care (SOC) multilayer compression dressings with an inactive wound contact layer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Venous Leg Ulcer (VLU)
- What is being tested?
- Topical Wound Oxygen Therapy
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 212 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jan 2025to Jun 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults ≥ 18 years and able to provide written informed consent
- Patients who have a chronic venous leg ulcer (VLU) below the knee at or above the malleolus determined to be due to underlying venous disease
- Venous reflux ≥ 500 mil sec/superficial or 1 sec/deep or venous mapping after interventions following a vascular procedure
- VLU of ≥ 1.5cm2 and ≤ 50cm2 after debridement at study enrolment i.e. Screening visit
- *Cluster wounds where the sum of the full thickness ulcer area must be ≤ 50cm2
- Study ulcer (current episode of ulceration in case of ulcer recurrence) has been present for at least 6 weeks but no more than 5 years prior to study entry
Show all 11Show fewer
- The index ulcer has been treated with CCD of at least 30mmHg for ≥ 6 weeks prior to screening.
- Adequate perfusion with Ankle-Brachial Pressure Index (ABPI) of 0.75-1.24 inclusive measured at study entry or within 8 weeks prior to study entry AND TcpO2 > 30mmHg OR Biphasic arterial duplex below the knee OR Toe pressure > 30mmHg OR TBI .6
- Wound size reduction in a 2-week run-in period of ≤ 30%
- Subject understands and is willing to participate in the clinical study and comply with weekly visits and follow up regime
- Subject has read and signed IRB/EC approved ICF before screening procedures commence
Who cannot join
- • Known allergy to any of the protocol-stipulated treatments, or non-tolerance of multilayer, multicomponent compression therapy
- Acute thrombophlebitis or Deep Vein Thrombosis (DVT) and within three months preceding study entry
- Subject awaiting venous ablation or is less than 30 days post ablation
- Surgery during three months prior to study entry (such as abdominal, gynecological, hip or knee replacement)
- Wound etiology of uncertain origin or history or prior diagnosis of Systemic Lupus Erythematosus, Burger's Disease, Pyoderma Gangrenosum or other inflammatory ulceration, vasculitis
- Documented evidence of osteomyelitis on any part of affected limb
Show all 19Show fewer
- Index ulcer has exposed bone, muscle and tendon
- Index ulcer exhibits signs of unmanaged wound infection or severe clinical infection that requires hospitalization or immediate surgical intervention
- BMI > 45
- Uncontrolled diabetes: HbA1c > 12% within 60 days of screening
- Renal dialysis or of screening EGFR less than 30 mg/dl
- NYHA Class IV
- Peripheral arterial reconstruction/revascularization on the affected limb within the last 30 days
- Any medication deemed by the Investigator to potentially interfere with the study treatment (e.g. systemic steroids > 10mg daily dose, immunosuppressive agents).
- Active systemic treatment for malignancy
- History of radiation at the ulcer site
- Subject has received growth factor therapy (e.g., autologous platelet-rich plasma gel, becaplermin, bilayer cell therapy, dermal substitute, extracellular matrix) within 14 days before screening
- Subject participated in another investigational device, drug or biological trial within four weeks prior to study entry
- Subject may not be pregnant or breastfeeding at the time of treatment
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Vascular Institute of New York
New York, New York, 10016
About this study
Official title: A Multi-national, Prospective, Randomized, Double Blinded, Placebo-controlled Trial to Evaluate Cyclical Topical Wound Oxygen Therapy (TWO2) in the Treatment of Chronic Venous Leg Ulcers
The purpose of this study is to evaluate the efficacy, safety and economic benefits of Cyclical Pressure Topical Wound Oxygen (TWO2) Therapy in the treatment of venous leg ulcers. Participants will utilize standard of care (SOC) multilayer compression dressings with an inactive wound contact layer. Following a 2-week run-in period with SOC and after meeting all eligibility criteria, subjects will be randomized in a 1:1 ratio with TWO2 therapy or sham control therapy plus SOC. Participants will enter the intervention period of up to 16-weeks, followed by a long-term follow-up period of 52 weeks post randomization.
Read the detailed description
The full effect of Venous leg ulcers (VLU) on society is poorly understood. While chronic VLU are not considered to have a significant impact on mortality, the burden on patients, caregivers, healthcare systems and related economies cannot be underestimated. VLU affects 2% of the world's population, with 60% progressing to chronic wounds. (1) The reported range of VLU incidence is 0.12 - 1.69% and with a prevalence 0.3 - 1.33%. (2; 3) VLUs are a result of chronic venous insufficiency (CVI) and found to be more prevalent in females than males, with both primary (genetic) and secondary causes that result in valvular incompetence that is further exacerbated by obesity and immobility. (4) With the projected growth of aging and increasingly obese and unhealthy societies, both in the developed and developing world, the anticipated incidence of VLU is expected to rise significantly. (1; 5; 6) It has been well established that the standard of care (SOC) for VLU is the application of conventional compression dressing (CCD), as the successful management of venous hypertension is key to healing VLU. Maintaining a mobile blood flow and delivering oxygen and nutrients to tissues is essential to healing as well as preserving the integrity of skin reducing threat of developing a recurrent VLU.
The role of oxygen in wound healing has been extensively studied. An animal study by Fries et al in 2005 demonstrated that the application of oxygen in partial pressures above those delivered by a well-functioning arterial system, to wounded tissue, resulted in faster healing and more durable tissue. (19) Oxygen is also essential in fighting infection, potentiating the use of antibiotics and upregulating growth factors. (20; 21) A study by Tawfick and Sultan in 2012 demonstrated a significant benefit in healing VLU when both oxygen and cycling compression were employed simultaneously. Utilizing Topical Wound Oxygen (TWO2) therapy™, TWO2 was demonstrated to be superior to SOC, 76% vs 46% healing at 12 weeks (n = 30/65; P < .0001), with low recurrence rates for patients followed up to three years, 6% vs 47%. Further noteworthy results from this study were the reduction of pain, 8 to 3 in 13 days (on a numerical rating scale) and subjects whose wounds were infected with MRSA demonstrated elimination 46% vs 0% at week 5 (P <.001). (22)
All subjects will use the TWO2/Sham device for a minimum of 120 minutes a day in their home (where the infrastructure supports remote therapy), 5 times a week for the treatment phase of up to 16 weeks. Monitoring of the wound will take place with bi-weekly clinic visits to assess safety, compliance, wound progression/deterioration, wound photographs and measurements.
The maximum duration for participation in the trial is 52 weeks (+/- 2 weeks). During the follow-up phase, subjects will receive standard care according to the clinician's recommendation and will be asked not to participate in another wound care trial during this period.
- Conditions
- Venous Leg Ulcer (VLU)
- Being tested
- Topical Wound Oxygen Therapy, Sham Control Topical Wound Oxygen
- Keywords
- Ulcer, Wound, Randomized, Oxygen, Placebo, Sham, Venous, Compression, Varicose Veins, Venous stasis ulcer, Topical Oxygen
- Medical subject headings
- Varicose Ulcer, Ulcer, Wounds and Injuries, Varicose Veins
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Topical Wound Oxygen TherapyDevice
The active intervention is the application of the Topical Wound Oxygen device that supplies cyclical oxygen pressure directly to the wound site within a sealed environment.
Sham Control Topical Wound OxygenDevice
The sham control intervention is the application of Topical Wound Oxygen device that supplies topical room air to the wound site within a sealed environment.
| Study group | Role | What they receive |
|---|---|---|
| Topical Wound Oxygen Therapy Device | Active comparator | Topical Wound Oxygen (TWO2) device in combination with the extremity chamber delivers oxygen and cyclical compression to the wound site. The sealed environment created by the extremity chamber is filled with oxygen for a minimum of 120 minutes, 5 times a week over multilayered compression dressings and a wound contact layer. Receives: Device: Topical Wound Oxygen Therapy |
| Sham Control Topical Wound Oxygen (TWO2) device | Sham comparator | A Sham Control Topical Wound Oxygen (TWO2) device in combination with the extremity chamber that does not deliver oxygen and cyclical compression to the wound site. The sealed environment created by the extremity chamber is filled with room air for a minimum of 120 minutes, 5 times a week over multilayered compression dressings and a wound contact layer. Receives: Device: Sham Control Topical Wound Oxygen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of complete wound closure within 16 weeks with the use of Topical Wound Oxygen Therapy (TWO2)
Percentage incidence of complete wound closure defined as 100% skin re-epithelialization without the need for wound dressing that is confirmed by 2 consecutive study visits 2 weeks apart.
Measured: From Baseline to16 weeks
Secondary outcomes (16)
Percentage Area Reduction (PAR)
Change in wound area will be documented bi-weekly by the use of digital photography and wound mapping
Measured: Baseline, Week 2, 4, 6, 8, 10, 12, 14 up to 16 weeks (± 2 days)
Incidence of complete wound closure at 12 weeks
Incidence of complete wound closure defined as 100% skin re-epithelialization without the need for wound dressing that is confirmed by 2 consecutive study visits 2 weeks apart.
Measured: From Baseline to12 weeks
Incidence of complete wound closure at 52 weeks
Incidence of complete wound closure defined as 100% skin re-epithelialization without the need for wound dressing that is confirmed by 2 consecutive study visits 2 weeks apart.
Measured: From week 16 to 52 weeks
Time to complete wound closure
Healing difference over Time will be assessed over a 16-week period
Measured: Baseline, Week 2, 4, 6, 8, 10, 12, 14 up to 16 weeks (± 2 days), 20, 26, 52 weeks (± 2 weeks)
Pain Visual Analog Scale (VAS) score
Pain scores documented on a weekly basis measured using a 0-10 Visual Analog Scale (VAS) score, with zero (0) indicating no pain and 10 indicating the worst possible pain.
Measured: Baseline weekly up to 16 weeks (±2 days)
Incidence of recurrence
Wounds documented as "healed" will be followed for incidence of recurrence. Count of wound recurrences of healed wounds. For healed wounds, VLU recurrence was collected via phone calls and subjects at follow up timelines.
Measured: From Baseline up to week 16, week 20, 26 (± 1 week), 52 (± 2 weeks)
Incidence of Adverse Events at 16 weeks
Total number of different types of adverse events in participants who reported with any untoward medical event
Measured: From Baseline to16 weeks
Incidence of Serious Adverse Events at 16 weeks
Total number of different types of serious adverse events in participants who reported that:
- results in death
- is life-threatening (places the subject at immediate risk of death from the experience as it occurred)
- results in a persistent or significant disability/incapacity (substantial disruption of one's ability to carry out normal life functions)
- results in medical or surgical intervention
- results in or prolongs an existing hospitalization (even if the hospitalization is a precautionary measure for observation)
Measured: From Baseline to16 weeks
Incidence of Serious Adverse Events at 52 weeks
Total number of different types of serious adverse events in participants who reported that:
- results in death
- is life-threatening (places the subject at immediate risk of death from the experience as it occurred)
- results in a persistent or significant disability/incapacity (substantial disruption of one's ability to carry out normal life functions)
- results in medical or surgical intervention
- results in or prolongs an existing hospitalization (even if the hospitalization is a precautionary measure for observation)
Measured: From 16 to 52 weeks
Change in Venous Clinical Severity Score (VCSS)
Mean change in Venous Clinical Severity Score (VCSS) from baseline to week 16. VCSS assesses nine common signs/symptoms of venous disease and each item is scored individually with a minimum score of "0" and maximum score of "3". The individual items are added together to assess change from baseline. Higher scores mean worst outcome.
Measured: From Baseline to 16 weeks
Elimination of Infection
Wound cultures will be taken at the Baseline visit then again at week 6. Wounds defined as "infected" at the baseline visit and "not infection" at weeks 6, are documented as wound infection elimination.
Measured: From Baseline to week 6
Change in Health-related Quality of Life (Venous Leg Ulcer Quality of life Questionnaire ~ (VLU-QoL-34))
Mean difference in change in Venous Leg Ulcer Quality of life Questionnaire ~ (VLU-QoL-34) from baseline to 16 weeks. Crude subscale scores for each group are not shown (each crude subscale is scored 1 to 5 at baseline and 16 weeks); higher mean differences in change from baseline to 16 weeks within groups indicate greater change on the subscales for that group.
Measured: From Baseline to week 8, up to week 16 (± 2 days)
Emotional distress
The emotional distress will be assessed through the total score of the Hospital Anxiety and Depression Scale, comprising both anxiety and depression scales (HADS; Pais-Ribeiro et al., 2007). Scores range between 0 and 42, with higher results indicating higher levels of distress.
Measured: From Baseline to week 8, up to week 16 (± 2 days)
Anxiety symptoms
The anxious symptomatology will be assessed through the Hospital Anxiety and Depression Scale (HADS; Pais-Ribeiro et al., 2007). Scores range between 0 and 21, with higher results indicating higher levels of anxiety symptoms.
Measured: From Baseline to week 8, up to week 16 (± 2 days)
Depression
The depressive symptomatology will be assessed through the Hospital Anxiety and Depression Scale (HADS; Pais-Ribeiro et al., 2007). Scores range between 0 and 21, with higher results indicating higher levels of depression symptoms.
Measured: From Baseline to week 8, up to week 16 (± 2 days)
Change in Health-related Quality of Life (EuroQol-5D 3L)
Mean difference in change measured by EuroQol 5D (EQ5D 3L) from baseline to 16 weeks. Crude health state scores for each group are not shown (health state is scored 0 to 100 at baseline and 16 weeks); higher mean differences in change from baseline to 16 weeks within groups indicate greater change on health state for that group.
Measured: From Baseline to week 8, up to week 16 (± 2 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jan 2025
- Study start15 Jan 2025
- Primary completionJun 2027 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Venous Leg Ulcer (VLU)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, Double Blinded, Placebo-controlled Trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 212 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AOTI Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mike Griffiths, DProf, DMS, CRT, FCMI, Study chair, AOTI Ltd.Anil Hingorani, MD, Principal investigatorWael Tawfick, MB.BCH, MRCSI., Principal investigator, University of Galway
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06754735
- Sponsor's protocol ID
- AOTI
- Acronym
- VaLUe I
- Status last verified
- Nov 2025
- First submitted
- 16 Dec 2024
- Last updated
- 19 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Frykberg RG, Franks PJ, Edmonds M, Brantley JN, Teot L, Wild T, Garoufalis MG, Lee AM, Thompson JA, Reach G, Dove CR, Lachgar K, Grotemeyer D, Renton SC; TWO2 Study Group. A Multinational, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy of Cyclical Topical Wound Oxygen (TWO2) Therapy in the Treatment of Chronic Diabetic Foot Ulcers: The TWO2 Study. Diabetes Care. 2020 Mar;43(3):616-624. doi: 10.2337/dc19-0476. Epub 2019 Oct 16.
PubMed 31619393Tawfick WA, Sultan S. Technical and clinical outcome of topical wound oxygen in comparison to conventional compression dressings in the management of refractory nonhealing venous ulcers. Vasc Endovascular Surg. 2013 Jan;47(1):30-7. doi: 10.1177/1538574412467684. Epub 2012 Dec 5.
PubMed 23223182Fowkes FG, Evans CJ, Lee AJ. Prevalence and risk factors of chronic venous insufficiency. Angiology. 2001 Aug;52 Suppl 1:S5-15. doi: 10.1177/0003319701052001S02.
PubMed 11510598
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-national, Prospective, Randomized, Double Blinded, Placebo-controlled Trial to Evaluate Cyclical Topical Wound Oxygen Therapy (TWO2) in the Treatment of Chronic Venous Leg Ulcers
- ClinicalTrials.gov ID
- NCT06754735
- Acronym / sponsor ID
- VaLUe I / AOTI
- Conditions
- Venous Leg Ulcer (VLU)
- Keywords
- Ulcer, Wound, Randomized, Oxygen, Placebo, Sham, Venous, Compression, Varicose Veins, Venous stasis ulcer, Topical Oxygen
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 212 participants (estimated)
- Lead sponsor
- AOTI Ltd.Industry (pharma, biotech, devices)
- Study start
- 15 Jan 2025 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 1 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy, safety and economic benefits of Cyclical Pressure Topical Wound Oxygen (TWO2) Therapy in the treatment of venous leg ulcers. Participants will utilize standard of care (SOC) multilayer compression dressings with an inactive wound contact layer. Following a 2-week run-in period with SOC and after meeting all eligibility criteria, subjects will be randomized in a 1:1 ratio with TWO2 therapy or sham control therapy plus SOC. Participants will enter the intervention period of up to 16-weeks, followed by a long-term follow-up period of 52 weeks post randomization.
Detailed description
The full effect of Venous leg ulcers (VLU) on society is poorly understood. While chronic VLU are not considered to have a significant impact on mortality, the burden on patients, caregivers, healthcare systems and related economies cannot be underestimated. VLU affects 2% of the world's population, with 60% progressing to chronic wounds. (1) The reported range of VLU incidence is 0.12 - 1.69% and with a prevalence 0.3 - 1.33%. (2; 3) VLUs are a result of chronic venous insufficiency (CVI) and found to be more prevalent in females than males, with both primary (genetic) and secondary causes that result in valvular incompetence that is further exacerbated by obesity and immobility. (4) With the projected growth of aging and increasingly obese and unhealthy societies, both in the developed and developing world, the anticipated incidence of VLU is expected to rise significantly. (1; 5; 6) It has been well established that the standard of care (SOC) for VLU is the application of conventional compression dressing (CCD), as the successful management of venous hypertension is key to healing VLU. Maintaining a mobile blood flow and delivering oxygen and nutrients to tissues is essential to healing as well as preserving the integrity of skin reducing threat of developing a recurrent VLU.
The role of oxygen in wound healing has been extensively studied. An animal study by Fries et al in 2005 demonstrated that the application of oxygen in partial pressures above those delivered by a well-functioning arterial system, to wounded tissue, resulted in faster healing and more durable tissue. (19) Oxygen is also essential in fighting infection, potentiating the use of antibiotics and upregulating growth factors. (20; 21) A study by Tawfick and Sultan in 2012 demonstrated a significant benefit in healing VLU when both oxygen and cycling compression were employed simultaneously. Utilizing Topical Wound Oxygen (TWO2) therapy™, TWO2 was demonstrated to be superior to SOC, 76% vs 46% healing at 12 weeks (n = 30/65; P < .0001), with low recurrence rates for patients followed up to three years, 6% vs 47%. Further noteworthy results from this study were the reduction of pain, 8 to 3 in 13 days (on a numerical rating scale) and subjects whose wounds were infected with MRSA demonstrated elimination 46% vs 0% at week 5 (P <.001). (22)
All subjects will use the TWO2/Sham device for a minimum of 120 minutes a day in their home (where the infrastructure supports remote therapy), 5 times a week for the treatment phase of up to 16 weeks. Monitoring of the wound will take place with bi-weekly clinic visits to assess safety, compliance, wound progression/deterioration, wound photographs and measurements.
The maximum duration for participation in the trial is 52 weeks (+/- 2 weeks). During the follow-up phase, subjects will receive standard care according to the clinician's recommendation and will be asked not to participate in another wound care trial during this period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, Double Blinded, Placebo-controlled Trial
| Arm | Type | Receives |
|---|---|---|
| Topical Wound Oxygen Therapy Device | Active comparator | Device: Topical Wound Oxygen TherapyTopical Wound Oxygen (TWO2) device in combination with the extremity chamber delivers oxygen and cyclical compression to the wound site. The sealed environment created by the extremity chamber is filled with oxygen for a minimum of 120 minutes, 5 times a week over multilayered compression dressings and a wound contact layer. |
| Sham Control Topical Wound Oxygen (TWO2) device | Sham comparator | Device: Sham Control Topical Wound OxygenA Sham Control Topical Wound Oxygen (TWO2) device in combination with the extremity chamber that does not deliver oxygen and cyclical compression to the wound site. The sealed environment created by the extremity chamber is filled with room air for a minimum of 120 minutes, 5 times a week over multilayered compression dressings and a wound contact layer. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Adults ≥ 18 years and able to provide written informed consent
- Patients who have a chronic venous leg ulcer (VLU) below the knee at or above the malleolus determined to be due to underlying venous disease
- Venous reflux ≥ 500 mil sec/superficial or 1 sec/deep or venous mapping after interventions following a vascular procedure
- VLU of ≥ 1.5cm2 and ≤ 50cm2 after debridement at study enrolment i.e. Screening visit
- *Cluster wounds where the sum of the full thickness ulcer area must be ≤ 50cm2
Key exclusion criteria (19 listed)
- • Known allergy to any of the protocol-stipulated treatments, or non-tolerance of multilayer, multicomponent compression therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Topical Wound Oxygen TherapyThe active intervention is the application of the Topical Wound Oxygen device that supplies cyclical oxygen pressure directly to the wound site within a sealed environment. | Device | Topical Wound Oxygen Therapy Device |
| Sham Control Topical Wound OxygenThe sham control intervention is the application of Topical Wound Oxygen device that supplies topical room air to the wound site within a sealed environment. | Device | Sham Control Topical Wound Oxygen (TWO2) device |
Primary outcome
Incidence of complete wound closure within 16 weeks with the use of Topical Wound Oxygen Therapy (TWO2)
Time frame: From Baseline to16 weeks
Percentage incidence of complete wound closure defined as 100% skin re-epithelialization without the need for wound dressing that is confirmed by 2 consecutive study visits 2 weeks apart.
16 secondary outcomes
Percentage Area Reduction (PAR)
Time frame: Baseline, Week 2, 4, 6, 8, 10, 12, 14 up to 16 weeks (± 2 days)
Incidence of complete wound closure at 12 weeks
Time frame: From Baseline to12 weeks
Incidence of complete wound closure at 52 weeks
Time frame: From week 16 to 52 weeks
Time to complete wound closure
Time frame: Baseline, Week 2, 4, 6, 8, 10, 12, 14 up to 16 weeks (± 2 days), 20, 26, 52 weeks (± 2 weeks)
Pain Visual Analog Scale (VAS) score
Time frame: Baseline weekly up to 16 weeks (±2 days)
Incidence of recurrence
Time frame: From Baseline up to week 16, week 20, 26 (± 1 week), 52 (± 2 weeks)
Incidence of Adverse Events at 16 weeks
Time frame: From Baseline to16 weeks
Incidence of Serious Adverse Events at 16 weeks
Time frame: From Baseline to16 weeks
Incidence of Serious Adverse Events at 52 weeks
Time frame: From 16 to 52 weeks
Change in Venous Clinical Severity Score (VCSS)
Time frame: From Baseline to 16 weeks
Elimination of Infection
Time frame: From Baseline to week 6
Change in Health-related Quality of Life (Venous Leg Ulcer Quality of life Questionnaire ~ (VLU-QoL-34))
Time frame: From Baseline to week 8, up to week 16 (± 2 days)
Emotional distress
Time frame: From Baseline to week 8, up to week 16 (± 2 days)
Anxiety symptoms
Time frame: From Baseline to week 8, up to week 16 (± 2 days)
Depression
Time frame: From Baseline to week 8, up to week 16 (± 2 days)
Change in Health-related Quality of Life (EuroQol-5D 3L)
Time frame: From Baseline to week 8, up to week 16 (± 2 days)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2025.
- Background: PubMed 31619393Frykberg RG, Franks PJ, Edmonds M, Brantley JN, Teot L, Wild T, Garoufalis MG, Lee AM, Thompson JA, Reach G, Dove CR, Lachgar K, Grotemeyer D, Renton SC; TWO2 Study Group. A Multinational, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy of Cyclical Topical Wound Oxygen (TWO2) Therapy in the Treatment of Chronic Diabetic Foot Ulcers: The TWO2 Study. Diabetes Care. 2020 Mar;43(3):616-624. doi: 10.2337/dc19-0476. Epub 2019 Oct 16.
- Background: PubMed 23223182Tawfick WA, Sultan S. Technical and clinical outcome of topical wound oxygen in comparison to conventional compression dressings in the management of refractory nonhealing venous ulcers. Vasc Endovascular Surg. 2013 Jan;47(1):30-7. doi: 10.1177/1538574412467684. Epub 2012 Dec 5.
- Background: PubMed 11510598Fowkes FG, Evans CJ, Lee AJ. Prevalence and risk factors of chronic venous insufficiency. Angiology. 2001 Aug;52 Suppl 1:S5-15. doi: 10.1177/0003319701052001S02.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mike Griffiths, DProf, DMS, CRT, FCMI study chair
AOTI Ltd.
Anil Hingorani, MD principal investigator
Wael Tawfick, MB.BCH, MRCSI. principal investigator
University of Galway
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Topical Wound Oxygen Therapy in people with Venous Leg Ulcer (VLU), run by AOTI Ltd. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Despina Herodotou, MRCPod, DABPMi (1-760-431-4700, despi.herodotou@aotinc.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of complete wound closure within 16 weeks with the use of Topical Wound Oxygen Therapy (TWO2) (time frame: From Baseline to16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06754735, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2025; AzTrials last refreshed its copy on 6 Nov 2026.